PMID- 12578975 OWN - NLM STAT- MEDLINE DCOM- 20030401 LR - 20231105 IS - 0027-8424 (Print) IS - 1091-6490 (Electronic) IS - 0027-8424 (Linking) VI - 100 IP - 4 DP - 2003 Feb 18 TI - Insights into glutamate transport regulation in human astrocytes: cloning of the promoter for excitatory amino acid transporter 2 (EAAT2). PG - 1955-60 AB - Glutamate transport is central to neurotransmitter functions in the brain. Impaired glutamate transport induces neurotoxicity associated with numerous pathological processes, including stroke/ischemia, temporal lobe epilepsy, Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, HIV-1-associated dementia, and growth of malignant gliomas. Excitatory amino acid transporter-2 (EAAT2) is a major glutamate transporter in the brain expressed primarily in astrocytes. We presently describe the cloning and characterization of the human EAAT2 promoter, demonstrating elevated expression in astrocytes. Regulators of EAAT2 transport, both positive and negative, alter EAAT2 transcription, promoter activity, mRNA, and protein. These findings imply that transcriptional processes can regulate EAAT2 expression. Moreover, they raise the intriguing possibility that the EAAT2 promoter may be useful for targeting gene expression in the brain and for identifying molecules capable of modulating glutamate transport that could potentially inhibit, ameliorate, or prevent various neurodegenerative diseases. FAU - Su, Zao-zhong AU - Su ZZ AD - Department of Pathology, Herbert Irving Comprehensive Cancer Center, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. FAU - Leszczyniecka, Magdalena AU - Leszczyniecka M FAU - Kang, Dong-chul AU - Kang DC FAU - Sarkar, Devanand AU - Sarkar D FAU - Chao, Wei AU - Chao W FAU - Volsky, David J AU - Volsky DJ FAU - Fisher, Paul B AU - Fisher PB LA - eng SI - GENBANK/AF510107 GR - P01 NS031492/NS/NINDS NIH HHS/United States GR - NS31492/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. DEP - 20030210 PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (DNA Primers) RN - 0 (Excitatory Amino Acid Transporter 2) RN - 0 (RNA, Messenger) RN - 3KX376GY7L (Glutamic Acid) SB - IM MH - Astrocytes/*metabolism MH - Base Sequence MH - Biological Transport MH - Cells, Cultured MH - Cloning, Molecular MH - DNA Primers MH - Excitatory Amino Acid Transporter 2/*genetics MH - Glutamic Acid/*metabolism MH - Humans MH - Molecular Sequence Data MH - *Promoter Regions, Genetic MH - RNA, Messenger/genetics/metabolism MH - Transcription, Genetic PMC - PMC149940 EDAT- 2003/02/13 04:00 MHDA- 2003/04/02 05:00 PMCR- 2003/08/18 CRDT- 2003/02/13 04:00 PHST- 2003/02/13 04:00 [pubmed] PHST- 2003/04/02 05:00 [medline] PHST- 2003/02/13 04:00 [entrez] PHST- 2003/08/18 00:00 [pmc-release] AID - 0136555100 [pii] AID - 6555 [pii] AID - 10.1073/pnas.0136555100 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1955-60. doi: 10.1073/pnas.0136555100. Epub 2003 Feb 10.